Quantification of Fuel Oxygenate Ethers in Human Blood using Solid-Phase Microextraction Coupled with Gas Chromatography-High-Resolution Mass Spectrometry

Abstract

Widespread use of fuel oxygenates, coupled with their high water solubility and slow degradation rate, have led to an increase in the potential for human exposure. We developed an accurate, precise, sensitive, and high-throughput analytical method to simultaneously quantify trace levels (low parts-per-trillion) of four fuel oxygenates in human blood: methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), di-isopropyl ether (DIPE), and tert-amyl methyl ether (TAME). The analytes were extracted from the head space above human blood samples, using solid-phase microextraction, desorbed into the heated injector, and chromatographically resolved by capillary gas chromatography. Analytes were detected by high-resolution mass spectrometry with multiple ion monitoring, and quantified against known standard levels by use of stable isotope-labeled internal standards for recovery correction. The low limits of detection (0.6 ng/L) allowed for measurement of MTBE, ETBE, DIPE, and TAME in parts-per-trillion levels with excellent precision (coefficient of variation ranging from 1.7 to 5.4%) and accuracy (96-100%). This method provides a means to assess fuel oxygenate exposure and study the potential relationship between exposure and adverse health outcomes.